Mitochondrially localized MPZL3 emerges as a signaling hub of mammalian physiology

• Published in: BioEssays Vol. 43; no. 10; pp. e2100126 - n/a
• Main Authors: Wikramanayake, Tongyu C., Nicu, Carina, Chéret, Jérémy, Czyzyk, Traci A., Paus, Ralf
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.10.2021
• Subjects: adipose tissue; Animals; Cell Differentiation; circadian clock; Circadian Rhythm; Circadian rhythms; Clock gene; CLOCK Proteins; Differentiation (biology); Energy expenditure; epidermal differentiation; Epithelial cells; Epithelium; genes; glycemic control; hair cycle; Hair Follicle; hair follicles; humans; Lipid metabolism; Lipids; Mammals; Membrane Proteins; Mice; Mice, Knockout; Mitochondria; Mitochondria - genetics; Peroxisome proliferator-activated receptors; phenotype; Phenotypes; Physiology; Sebaceous gland; Sebaceous glands; Signaling; Transcription factors; epidermal differentiation; adipose tissue; sebaceous gland; hair cycle; circadian clock; mitochondria
• ISSN: 0265-9247; 1521-1878; 1521-1878
• DOI: 10.1002/bies.202100126

MPZL3 is a nuclear‐encoded, mitochondrially localized, immunoglobulin‐like V‐type protein that functions as a key regulator of epithelial cell differentiation, lipid metabolism, ROS production, glycemic control, and energy expenditure. Recently, MPZL3 has surfaced as an important modulator of sebaceous gland function and of hair follicle cycling, an organ transformation process that is also governed by peripheral clock gene activity and PPARγ. Given the phenotype similarities and differences between Mpzl3 and Pparγ knockout mice, we propose that MPZL3 serves as a signaling hub that is regulated by core clock gene products and/or PPARγ to translate signals from these nuclear transcription factors to the mitochondria to modulate circadian and metabolic regulation. Conservation between murine and human MPZL3 suggests that human MPZL3 may have similarly complex functions in health and disease. We summarize current knowledge and discuss future directions to elucidate the full spectrum of MPZL3 functions in mammalian physiology. MPZL3 has emerged as a key regulator of the peripheral clock during hair follicle cycling and lipid metabolism. We propose that MPZL3 functions as a signaling hub that is regulated by core clock gene products and/or PPARγ to translate signals to the mitochondria to modulate circadian and metabolic regulation.